OVERALL OBJECTIVE: The long term objective of this project is to understand the genetic and epigenetic mechanisms by which the tumor cell regulates the expression of its tumor-specific antigens. To accomplish this objective, somatic genetic analysis is being used to study the number, dominance, and nature of the genes controlling the expression of several model surface antigens. Antigenic variants of murine lymphomas growing in tissue culture are being used as the experimental system. GOAL FOR 1976: 1. Derive and characterize additional Thy-1 variants of murine lymphomas in an attempt to identify additional genes involved in Thy-1 synthesis. 2. Study Thy-1 expression in fusions to tumor cells representing cells in other stages of differentiation (not expressing Thy-1). 3. Continue genetic studies on the TL antigen: (a) Derive and characterize additional TL- variants of lymphomas. (b) Study activation of TL specificities in fusions of lymphomas with normal thymocytes. BIBLIOGRAPHIC REFERENCES: Hyman, R. and Kelleher, R. (1975). Absence of Thy-1 antigen in L-Cell X mouse lymphoma hybrids. Somatic Cell Genet. 1: 335-343. Trowbridge, I. and Hyman, R. (1975). Thy-1 variants of mouse lymphomas. Biochemical characterization of the genetic defect. Cell 6: 279-287.